1. Field
The present disclosure relates to anti-inflammatory proteins, their uses, and methods of their detection.
2. Related Art
Honey has been used for centuries by cultures through the world for its multiple health benefits. Two of the most important health benefits of honey are its anti-bacterial and anti-inflammatory properties. Manuka honey, which is produced by bees that collect nectar from Leptospermum scoparium, a plant native to New Zealand and southern Australia, has been identified as being a variety of honey that exhibits particularly effective anti-bacterial and anti-inflammatory properties.
Recently, it was discovered that the chemical, methylglyoxal (MGO/2-oxopropanal), is a major component of the anti-bacterial activity of manuka honey. Manuka honey samples that contain greater concentrations of MGO have a higher amount of anti-bacterial activity as compared to honey samples with lower concentrations of MGO. MGO is believed to confer antibacterial properties on honey because MGO is a highly chemically reactive compound, and MGO can readily react with cellular molecules. The chemical reactions between MGO and cellular molecules in bacteria damage molecules that are important for bacterial viability, and thereby MGO functions as an antibacterial agent.
The presence of high levels of MGO in the honey is a feature that distinguishes manuka honey from other varieties of honey. While most varieties of honey exhibit some anti-bacterial activity, the anti-bacterial activity in most varieties of honey is primarily a result of the presence of hydrogen peroxide in the honey. Manuka honey, in contrast, exhibits anti-bacterial activity primarily because of the presence of MGO in the honey.
In 2004, Kohno et. al. examined the anti-inflammatory effects or actions of royal jelly at a cytokine level. The study results suggest that royal jelly has anti-inflammatory actions brought about by an inhibition of the proinflammatory cytokine production, such as TNF-α, IL-6 and IL-1, by activated macrophages. The study further suggested that the active fractions or components from the royal jelly were between 5 kDa and 30 kDa molecular weights. This study perhaps explains why most honeys have a weak anti-inflammatory effect because of the royal jelly proteins that occur in honey.
While multiple mechanisms of action of the anti-bacterial activity of manuka honey are understood, the mechanisms whereby manuka honey functions as an anti-inflammatory agent have remained unknown. There is a need to develop anti-inflammatory agents based on honey, because many anti-inflammatory agents currently available have major drawbacks to their use. For example, COX-2 inhibitors, a form of non-steroidal anti-inflammatory drug (NSAID), may increase the risk of heart attack and stroke in patients, and aspirin may increase the risk of gastrointestinal bleeding. Additionally, corticosteroids are reported to inhibit the growth of epithelial cells and NSAID's are reported as being cytotoxic so both of these classes of anti-inflammatory agents are unsuitable for use in wound care. Anti-inflammatory agents derived from honey may have fewer toxic side effects in one or more areas than drugs currently available, and may also offer different possible uses than anti-inflammatory drugs currently available.
In addition to the need for the development of anti-inflammatory drugs based on honey, there is also a need to develop a simple method to test the anti-inflammatory characteristics of a sample of honey. This disclosure addresses both of these and other unmet needs.
The inventors have identified a modified apalbumin of approximately 55-75 kDa from Manuka honey that results from the high levels of methylglyoxal found in Manuka honey. The inventors have identified that the modified apalbumin has significantly greater anti-inflammatory properties than an unmodified apalbumin.